Flavonoid Silibinin Increases Hair-Inductive Property Via Akt and Wnt/β-Catenin Signaling Activation in 3-Dimensional-Spheroid Cultured Human Dermal Papilla Cells

Hair loss, also known as alopecia, is a common dermatological condition of psychosocial significance; development of therapeutic candidates for the treatment of this condition is, hence, important. Silibinin, a secondary metabolite from Silybum marianum, is an effective antioxidant that also prevents various cutaneous problems. In this study, we have investigated the effect of silibinin on hair induction using three-dimensional (3D) cultured, human dermal papilla (DP) spheroids. Silibinin was found to significantly increase viability through AKT serine/threonine kinase (AKT) activation in 3D DP spheroids. This was correlated with an increase in the diameter of the 3D DP spheroids. The activation of the wingless and INT-1 (Wnt)/β-catenin signaling pathway, which is associated with hair growth induction in the DP, was evaluated using the T cell-specific transcription factor and lymphoid enhancer-binding factor (TCF/LEF) transcription factor reporter assay; results indicated significantly increased luciferase activity. In addition, we were able to demonstrate increased expression of the target genes, WNT5a and LEF1, using quantitative real-time PCR assay. Lastly, significantly elevated expression of signature genes associated with hair induction was demonstrated in the 3D DP spheroids treated with silibinin. These results suggest that silibinin promotes proliferation and hair induction through the AKT and Wnt/β-catenin signaling pathways in 3D DP spheroids. Silibinin can be a potential candidate to promote hair proliferation.